Ignite Creation Date:
2025-12-24 @ 11:08 PM
Ignite Modification Date:
2025-12-29 @ 12:29 PM
Study NCT ID:
NCT03647969
Status:
COMPLETED
Last Update Posted:
2024-08-09
First Post:
2018-06-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Modified FOLFOX Plus/Minus Nivolumab and Ipilimumab vs. FLOT Plus Nivolumab in Patients With Previously Untreated Advanced or Metastatic Gastric Cancer
Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Organization:
Study Overview
Official Title:
Modified FOLFOX Plus/Minus Nivolumab and Ipilimumab vs. FLOT Plus Nivolumab in Patients With Previously Untreated Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction - A Randomized Phase 2 Trial.
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients with Her2 negative, previously untreated metastatic esophagogastric adenocarcinoma will be treated with modified FOLFOX, with modified FOLFOX plus Nivolumab and Ipilimumab or FLOT plus Nivolumab. The groups will be compared for time until progression of the disease (primary endpoint) as well as for response to the treatment, overall survival, safety/tolerability of the treatment and quality of life.
Detailed Description:
This is a randomized, open labelled multicenter phase II trial, followed by a non-randomized arm.
Patients with Her2 negative, previously untreated metastatic esophagogastric adenocarcinoma will be randomized to receive either modified FOLFOX (Oxaliplatin at a dose of 85 mg/m² iv over two hours (day 1), Leucovorin at a dose of 400 mg/m2 iv over two hours (day 1), Fluorouracil at a dose of 400 mg/m² iv bolus (day 1), and Fluorouracil at a dose of 2400 mg/m² iv continuous infusion over 44 hours (day 1+2), every 2 weeks) alone, modified FOLFOX plus Nivolumab (240mg "Flatdose" i.v. d1 every 2 weeks) and Ipilimumab (1mg/kg i.v. d1 every 6 weeks) or sequential treatment (three cycles of induction chemotherapy with modified FOLFOX followed by immunotherapy consisting of 4 administrations of Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks and 2 administrations of Ipilimumab at 1mg/kg i.v. d1 every 6 weeks, this sequence may be repeated starting two weeks after last administration of immunotherapy once, or, if medically reasonable, for an unlimited number of repetitions upon investigator decision; after completion or discontinuation of chemotherapy, immunotherapy will be continued consisting of Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks and Ipilimumab at 1mg/kg i.v. d1 every 6 weeks). In a non-randomized arm, patients receive Nivolumab 240mg "Flatdose" i.v. d1 every 2 weeks and FLOT (Docetaxel 50mg/², Oxaliplatin 85 mg/m², leucovorin 200 mg/m² on day 1 and fluorouracil 2600 mg/m² IV continuous infusion over 24 hours) every 2 weeks. After completion or discontinuation of chemotherapy, immunotherapy may be continued (Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks).
Treatment in every arm will be given for a maximum of 24 months or until disease progression or inacceptable toxicity or end of study treatment.
The primary objective is to determine the clinical performance of the experimental regimen in patients with previously untreated HER2 negative locally advanced or metastatic esophagogastric adenocarcinoma in terms of progression free survival (acc. to RECIST v1.1).
Secondary objectives are to determine efficacy in terms of objective response rate (acc. to RECIST v1.1) and overall survival, as well as tolerability (acc. to NCI CTC AE v4.03) of the experimental regimen. In addition histopathological types and molecular parameters such as immune cell composition and PD-L1 expression as determined by quantitative mRNA (RT-PCR) will be correlated with efficacy in an exploratory analysis.
257 subjects (59 in the control arm, 89 in the experimental treatment group A1, 59 in the experimental treatment group A2 and 50 in the experimental treatment group C) will be enrolled.
Patients with Her2 negative, previously untreated metastatic esophagogastric adenocarcinoma will be randomized to receive either modified FOLFOX (Oxaliplatin at a dose of 85 mg/m² iv over two hours (day 1), Leucovorin at a dose of 400 mg/m2 iv over two hours (day 1), Fluorouracil at a dose of 400 mg/m² iv bolus (day 1), and Fluorouracil at a dose of 2400 mg/m² iv continuous infusion over 44 hours (day 1+2), every 2 weeks) alone, modified FOLFOX plus Nivolumab (240mg "Flatdose" i.v. d1 every 2 weeks) and Ipilimumab (1mg/kg i.v. d1 every 6 weeks) or sequential treatment (three cycles of induction chemotherapy with modified FOLFOX followed by immunotherapy consisting of 4 administrations of Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks and 2 administrations of Ipilimumab at 1mg/kg i.v. d1 every 6 weeks, this sequence may be repeated starting two weeks after last administration of immunotherapy once, or, if medically reasonable, for an unlimited number of repetitions upon investigator decision; after completion or discontinuation of chemotherapy, immunotherapy will be continued consisting of Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks and Ipilimumab at 1mg/kg i.v. d1 every 6 weeks). In a non-randomized arm, patients receive Nivolumab 240mg "Flatdose" i.v. d1 every 2 weeks and FLOT (Docetaxel 50mg/², Oxaliplatin 85 mg/m², leucovorin 200 mg/m² on day 1 and fluorouracil 2600 mg/m² IV continuous infusion over 24 hours) every 2 weeks. After completion or discontinuation of chemotherapy, immunotherapy may be continued (Nivolumab at 240mg "Flatdose" i.v. d1 every 2 weeks).
Treatment in every arm will be given for a maximum of 24 months or until disease progression or inacceptable toxicity or end of study treatment.
The primary objective is to determine the clinical performance of the experimental regimen in patients with previously untreated HER2 negative locally advanced or metastatic esophagogastric adenocarcinoma in terms of progression free survival (acc. to RECIST v1.1).
Secondary objectives are to determine efficacy in terms of objective response rate (acc. to RECIST v1.1) and overall survival, as well as tolerability (acc. to NCI CTC AE v4.03) of the experimental regimen. In addition histopathological types and molecular parameters such as immune cell composition and PD-L1 expression as determined by quantitative mRNA (RT-PCR) will be correlated with efficacy in an exploratory analysis.
257 subjects (59 in the control arm, 89 in the experimental treatment group A1, 59 in the experimental treatment group A2 and 50 in the experimental treatment group C) will be enrolled.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: